SARS-CoV 2NCT04368897
In-vitro Diagnostic Test to Predict COVID-19 Mortality and Disease Severity
An observational study of SARS-CoV 2 and COVID, run by Applied Biology, Inc. at 1 site in Spain.
Trial summary
The COVID-19 Androgen Sensitivity Test is a non-invasive In-Vitro Diagnostic device that utilizes Next Generation Sequencing Technology (NGS). The results of the test are used by a physician to assess the risk of developing severe symptoms following COVID-19 infection, The COVID-19 Androgen Sensitivity Test requires a… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- SARS-CoV 2, COVID, COVID-19
- What is being tested?
- CAG length <22 and CAG length >=22
- How many people
- 0 participants
- Where
- 1 siteSpain
- Study dates
- 1 May 2020to 1 Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- Adult, Older adult
Study population: Patients admitted to the hospital due to COVID-19
Who may be able to join
- Male over the age of 18
- First time present at the site
- Laboratory confirmed SARS-CoV-2 infection
- Able to give informed consent
Who cannot join
- Unable to give informed consent
- Diagnosed with an additional respiratory co-infection
- XXY males
Trial locations and contacts
1 site in 1 country.
About this study
The COVID-19 Androgen Sensitivity Test is a non-invasive In-Vitro Diagnostic device that utilizes Next Generation Sequencing Technology (NGS). The results of the test are used by a physician to assess the risk of developing severe symptoms following COVID-19 infection, The COVID-19 Androgen Sensitivity Test requires a health care professional to collect a DNA sample using an FDA cleared DNA sample collection kit.
Read the detailed description
In late 2019, a novel coronavirus, subsequently named SARS-CoV-2 (COVID-19), was first reported in Hubei province in China. Since it was first reported, a worldwide pandemic has ensued affecting more than 450,000 individuals as of March 2020. In the midst of the pandemic, epidemiological reports unveiled a disproportionate low rate of severe cases among adult females compared to adult males, 42% and 58%, respectively. Similarly, the rate of severe cases among pre-pubescent children was exceptionally low at 0.6%. An explanation for the skewed prevalence of severe COVID-19 infection in adult males has yet to be elucidated.
In newborns, it has long been recognized that male infants are more susceptible to respiratory distress syndrome and less likely to respond to prenatal glucocorticoid therapy to protect against respiratory distress. Respiratory distress is intimately tied to the production of pulmonary surfactant, e.g., pulmonary surfactant proteins have been demonstrated to protect against influenza A. In animal studies, it was demonstrated that a sexual dimorphism in fetal pulmonary surfactant production is influenced by the androgen receptor (AR). For example, in rabbits, dihydrotestosterone was shown to inhibit fetal pulmonary surfactant production in both males and females while an anti-androgen, flutamide, was demonstrated to remove the sexual dimorphism in surfactant production. While severe COVID-19 symptoms are primarily manifested in older adults, the similar sexual dimorphism in the severity of respiratory disease is of interest. In addition, AR expression is low prior to pubertal maturation and may contribute to the low incidence of severe COVID-19 infection in children. As such, the investigators propose that the lower rate of severe COVID-19 infection in female patients may be attributed to lower androgen receptor expression.
Additional evidence to the possible implication of androgens in COVID-19 infection severity is found in the molecular mechanism required for SARS-CoV-2 infectivity. SARS-CoV-2 is part of the coronavirus family of viruses including SARS-CoV-1 and MERS-CoV. Coronavirus predominantly infects type II pneumocytes in the human lung. Previously, it was demonstrated that SARS-CoV-2 cell entry depends on priming of a viral spike surface protein by transmembrane protease serine 2 (TMPRSS2) present in the host. In type II pneumocytes, TMPRSS2 expression is associated with an increase in androgen receptor (AR) expression, specifically connecting AR expression to SARS-CoV-2, due to AR-regulated TMPRSS2 gene promoter. Moreover, angiotensin converting enzyme 2 (ACE2) has been recognized as the attachment molecule to the viral spike surface protein, thus termed the "receptor of SARS-CoV-2". Interestingly, ACE2 has been shown to have reduced activity by the decrease of androgen hormones (experimental orchidectomy), possibly by decreased expression of ACE2.
A well known polymorphism of the androgen receptor is a CAG repeat in the first exon of AR gene. The number of CAG repeats has been correlated with AR function and expression. The primary purpose of this study is to evaluate the association of AR gene polymorphisms with disease severity and mortality following COVID-19 infection. If an association can be elucidated, it would imply novel treatment modalities. For example, the activation of AR can be reduced by several classes of drugs including androgen receptor antagonists, androgen synthesis inhibitors and antigonadotropins.
- Conditions
- SARS-CoV 2, COVID, COVID-19, Androgenetic Alopecia, Androgen Receptor Abnormal, Androgen Deficiency
- Being tested
- CAG length <22, CAG length >=22
- Medical subject headings
- COVID-19, Alopecia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAG length <22Diagnostic test
Also called Genetic Test - Short CAG Allele
CAG repeat length in exon 1 of AR gene
CAG length >=22Diagnostic test
Also called Genetic Test - Long CAG Allele
CAG repeat length in exon 1 of AR gene
| Study group | Role | What they receive |
|---|---|---|
| COVID-19 Male Patients | Males with laboratory confirmed SARS-CoV-2 infection Receives: Diagnostic Test: CAG length <22; Diagnostic Test: CAG length >=22 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hospital-free days to Day 28 [ Time Frame: 28 days]
Defined as 28 days minus the number of days from randomization to discharge home. If a patient has not been discharged home prior to day 28 or dies prior to day 28, hospital free days will be zero.
Measured: 28 days
1. Severity of Disease
Defined as discharged, hospitalization, admission to intensive care unit [ICU] and death
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2020
- Study start1 May 2020
- Primary completion1 Dec 2022
- Study completion1 Dec 2022
Why it stopped: Not able to recruit subjects
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for SARS-CoV 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Applied Biology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hospital Universitario Ramon y Cajal
- Responsible party
- Sponsor
- Investigators
- Sabina Herrera, MD, Principal investigator, Hospital Universitario Ramon y CajalCarlos Wambier, MD, Study director, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04368897
- Sponsor's protocol ID
- AB-IVD-CoV-001
- Status last verified
- Feb 2022
- First submitted
- 27 Apr 2020
- Last updated
- 19 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Goren A, McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Dhurat R, Washenik K, Lotti T. What does androgenetic alopecia have to do with COVID-19? An insight into a potential new therapy. Dermatol Ther. 2020 Jul;33(4):e13365. doi: 10.1111/dth.13365. Epub 2020 Apr 8. No abstract available.
PubMed 32237190Wambier CG, Goren A. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated. J Am Acad Dermatol. 2020 Jul;83(1):308-309. doi: 10.1016/j.jaad.2020.04.032. Epub 2020 Apr 10.
PubMed 32283245Goren A, Vano-Galvan S, Wambier CG, McCoy J, Gomez-Zubiaur A, Moreno-Arrones OM, Shapiro J, Sinclair RD, Gold MH, Kovacevic M, Mesinkovska NA, Goldust M, Washenik K. A preliminary observation: Male pattern hair loss among hospitalized COVID-19 patients in Spain - A potential clue to the role of androgens in COVID-19 severity. J Cosmet Dermatol. 2020 Jul;19(7):1545-1547. doi: 10.1111/jocd.13443. Epub 2020 Apr 23.
PubMed 32301221McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Sinclair R, Ramos PM, Washenik K, Andrade M, Herrera S, Goren A. Racial variations in COVID-19 deaths may be due to androgen receptor genetic variants associated with prostate cancer and androgenetic alopecia. Are anti-androgens a potential treatment for COVID-19? J Cosmet Dermatol. 2020 Jul;19(7):1542-1543. doi: 10.1111/jocd.13455. Epub 2020 Jun 14. No abstract available.
PubMed 32333494
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In-vitro Diagnostic Test to Predict COVID-19 Mortality and Disease Severity
- ClinicalTrials.gov ID
- NCT04368897
- Acronym / sponsor ID
- AB-IVD-CoV-001
- Conditions
- SARS-CoV 2, COVID, COVID-19, Androgenetic Alopecia, Androgen Receptor Abnormal, Androgen Deficiency
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Not able to recruit subjects
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Applied Biology, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Hospital Universitario Ramon y Cajal
- Study start
- 1 May 2020 (actual)
- Primary completion
- 1 Dec 2022 (actual)
- Study completion
- 1 Dec 2022 (actual)
- First posted
- 30 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The COVID-19 Androgen Sensitivity Test is a non-invasive In-Vitro Diagnostic device that utilizes Next Generation Sequencing Technology (NGS). The results of the test are used by a physician to assess the risk of developing severe symptoms following COVID-19 infection, The COVID-19 Androgen Sensitivity Test requires a health care professional to collect a DNA sample using an FDA cleared DNA sample collection kit.
Detailed description
In late 2019, a novel coronavirus, subsequently named SARS-CoV-2 (COVID-19), was first reported in Hubei province in China. Since it was first reported, a worldwide pandemic has ensued affecting more than 450,000 individuals as of March 2020. In the midst of the pandemic, epidemiological reports unveiled a disproportionate low rate of severe cases among adult females compared to adult males, 42% and 58%, respectively. Similarly, the rate of severe cases among pre-pubescent children was exceptionally low at 0.6%. An explanation for the skewed prevalence of severe COVID-19 infection in adult males has yet to be elucidated.
In newborns, it has long been recognized that male infants are more susceptible to respiratory distress syndrome and less likely to respond to prenatal glucocorticoid therapy to protect against respiratory distress. Respiratory distress is intimately tied to the production of pulmonary surfactant, e.g., pulmonary surfactant proteins have been demonstrated to protect against influenza A. In animal studies, it was demonstrated that a sexual dimorphism in fetal pulmonary surfactant production is influenced by the androgen receptor (AR). For example, in rabbits, dihydrotestosterone was shown to inhibit fetal pulmonary surfactant production in both males and females while an anti-androgen, flutamide, was demonstrated to remove the sexual dimorphism in surfactant production. While severe COVID-19 symptoms are primarily manifested in older adults, the similar sexual dimorphism in the severity of respiratory disease is of interest. In addition, AR expression is low prior to pubertal maturation and may contribute to the low incidence of severe COVID-19 infection in children. As such, the investigators propose that the lower rate of severe COVID-19 infection in female patients may be attributed to lower androgen receptor expression.
Additional evidence to the possible implication of androgens in COVID-19 infection severity is found in the molecular mechanism required for SARS-CoV-2 infectivity. SARS-CoV-2 is part of the coronavirus family of viruses including SARS-CoV-1 and MERS-CoV. Coronavirus predominantly infects type II pneumocytes in the human lung. Previously, it was demonstrated that SARS-CoV-2 cell entry depends on priming of a viral spike surface protein by transmembrane protease serine 2 (TMPRSS2) present in the host. In type II pneumocytes, TMPRSS2 expression is associated with an increase in androgen receptor (AR) expression, specifically connecting AR expression to SARS-CoV-2, due to AR-regulated TMPRSS2 gene promoter. Moreover, angiotensin converting enzyme 2 (ACE2) has been recognized as the attachment molecule to the viral spike surface protein, thus termed the "receptor of SARS-CoV-2". Interestingly, ACE2 has been shown to have reduced activity by the decrease of androgen hormones (experimental orchidectomy), possibly by decreased expression of ACE2.
A well known polymorphism of the androgen receptor is a CAG repeat in the first exon of AR gene. The number of CAG repeats has been correlated with AR function and expression. The primary purpose of this study is to evaluate the association of AR gene polymorphisms with disease severity and mortality following COVID-19 infection. If an association can be elucidated, it would imply novel treatment modalities. For example, the activation of AR can be reduced by several classes of drugs including androgen receptor antagonists, androgen synthesis inhibitors and antigonadotropins.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| COVID-19 Male Patients | – | Diagnostic Test: CAG length <22, Diagnostic Test: CAG length >=22Males with laboratory confirmed SARS-CoV-2 infection |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Age groups
- Adult, Older adult
- Study population
- Patients admitted to the hospital due to COVID-19
Key inclusion criteria (4 listed)
- Male over the age of 18
- First time present at the site
- Laboratory confirmed SARS-CoV-2 infection
- Able to give informed consent
Key exclusion criteria (3 listed)
- Unable to give informed consent
- Diagnosed with an additional respiratory co-infection
- XXY males
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CAG length <22Also: Genetic Test - Short CAG AlleleCAG repeat length in exon 1 of AR gene | Diagnostic test | COVID-19 Male Patients |
| CAG length >=22Also: Genetic Test - Long CAG AlleleCAG repeat length in exon 1 of AR gene | Diagnostic test | COVID-19 Male Patients |
Primary outcome
Hospital-free days to Day 28 [ Time Frame: 28 days]
Time frame: 28 days
Defined as 28 days minus the number of days from randomization to discharge home. If a patient has not been discharged home prior to day 28 or dies prior to day 28, hospital free days will be zero.
1. Severity of Disease
Time frame: Day 28
Defined as discharged, hospitalization, admission to intensive care unit [ICU] and death
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2023.
- Results publication: PubMed 32237190Goren A, McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Dhurat R, Washenik K, Lotti T. What does androgenetic alopecia have to do with COVID-19? An insight into a potential new therapy. Dermatol Ther. 2020 Jul;33(4):e13365. doi: 10.1111/dth.13365. Epub 2020 Apr 8. No abstract available.
- Results publication: PubMed 32283245Wambier CG, Goren A. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated. J Am Acad Dermatol. 2020 Jul;83(1):308-309. doi: 10.1016/j.jaad.2020.04.032. Epub 2020 Apr 10.
- Results publication: PubMed 32301221Goren A, Vano-Galvan S, Wambier CG, McCoy J, Gomez-Zubiaur A, Moreno-Arrones OM, Shapiro J, Sinclair RD, Gold MH, Kovacevic M, Mesinkovska NA, Goldust M, Washenik K. A preliminary observation: Male pattern hair loss among hospitalized COVID-19 patients in Spain - A potential clue to the role of androgens in COVID-19 severity. J Cosmet Dermatol. 2020 Jul;19(7):1545-1547. doi: 10.1111/jocd.13443. Epub 2020 Apr 23.
- Results publication: PubMed 32333494McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Sinclair R, Ramos PM, Washenik K, Andrade M, Herrera S, Goren A. Racial variations in COVID-19 deaths may be due to androgen receptor genetic variants associated with prostate cancer and androgenetic alopecia. Are anti-androgens a potential treatment for COVID-19? J Cosmet Dermatol. 2020 Jul;19(7):1542-1543. doi: 10.1111/jocd.13455. Epub 2020 Jun 14. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sabina Herrera, MD principal investigator
Hospital Universitario Ramon y Cajal
Carlos Wambier, MD study director
Brown University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of SARS-CoV 2 and COVID, run by Applied Biology, Inc. at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 19 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hospital-free days to Day 28 [ Time Frame: 28 days] (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04368897, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2023.